Disposition of ¹⁴C-loprazolam in animals and man

Abstract

1. The disposition of ¹⁴C-loprazolam has been studied in rat, dog, cynomolgus monkey and man using oral and parenteral dosing. In all species ¹⁴C was excreted principally in the faeces irrespective of the route of administration.

2. In surgically prepared animals, 46% dose (rat) or 60% (dog) was excreted in bile and, together with urinary excretion, indicates that approx, two-thirds of an oral dose was absorbed. In rat there was relatively little enterohepatic circulation (~26%) compared to dog (~73%).

3. Whole-body autoradiography and tissue-distribution studies in rat showed that ¹⁴C was distributed principally in liver and intestine, and was eliminated within 24 h. ¹⁴C was found in brain of rat and dog; in dog concn. levels were higher in white matter than in grey matter.

4. In studies using pigmented animals, ¹⁴C was associated with the uveal tract of the eye and with other melanin-containing tissues. This was reversible and was eliminated from the eye of rat with a half-life of 3.4 d.

5. Blood and plasma concn. of ¹⁴C and of unchanged loprazolam declined relatively rapidly in rat. In dog, cynomolgus monkey and man, total ¹⁴C concn. in blood fell more slowly than unchanged loprazolam. Less than 85% of loprazolam was protein bound in rat, dog or human plasma in vitro.